We propose research which will provide information on the effects of reduced-coronary flow ischemia on capillary-tissue transport in the heart. We will study the effects of ischemia on the relationships among coronary flow distribution, coronary sinus lactic acid content, epicardial electrograms, coronary flow resistance and coronary capillary exchange as documented by a multiple-tracer technique. Studies will be performed in open-chest anesthetized and heparinized dogs. Flow and pressure in the left anterior descending (LAD) coronary artery will be measured and controlled through a silastic tubing cannula which connects the left carotid artery to the LAD. Capillary-tissue transport of small molecules will be documented by the bolus injection of a mixture of indicators (51Cr-red blood cells, 125I-albumin, 14C-sucrose and 3H-water) into the LAD cannula with sampling from the coronary sinus. The resulting multiple-tracer curves will be alalyzed mathematically for sucrose microvascular permeability surface area (PS) and the extravascular volume of distribution of sucrose and water. Flow distribution will be measured by the injection of labelled microspheres into the left atrium and the cannula. Protein transport will be measured by collecting cardiac lymph and analyzing its protein content. The effects of adenosine, phenoxybenzamine, histamine, antihistamine, heparin and hyaluronidase on capillary transport in the presence of ischemia will be measured. This should provide information on the relative importance of autoregulation, neural regulation and transport on the deterioration of flow in an ischemic segment after flow-reduction. Further, information on the relationship between hyaluronidase action and endogenous histamine release will be sought through combined infusions of hyaluronidase and antihistamines. The effects of heparin on hyaluronidase action will be tested by comparing infusion of hyaluronidase in dogs anticoagulated with coumarin to those anticoagulated with heparin. These studies should provide useful information on the relationship between coronary capillary-tissue transport, ischemia and drugs which may affect ischemia by altering transport.